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At least 343 records · Page 19Linked to original sources
PubMed2005

Dexrazoxane : a review of its use for cardioprotection during anthracycline chemotherapy.

Dexrazoxane (Cardioxane, Zinecard, a cyclic derivative of edetic acid, is a site-specific cardioprotective agent that effectively protects against anthracycline-induced cardiac toxicity. Dexrazoxane is approved in the US and some European countries for cardioprotection in women with advanced and/or metastatic breast cancer receiving doxorubicin; in other countries dexrazoxane is approved for use in a wider range of patients with advanced cancer receiving anthracyclines. As shown in clinical trials, intravenous dexrazoxane significantly reduces the incidence of anthracycline-induced congestive heart failure (CHF) and adverse cardiac events in women with advanced breast cancer or adults with soft tissue sarcomas or small-cell lung cancer, regardless of whether the drug is given before the first dose of anthracycline or the administration is delayed until cumulative doxorubicin dose is > or =300 mg/m2. The drug also appears to offer cardioprotection irrespective of pre-existing cardiac risk factors. Importantly, the antitumour efficacy of anthracyclines is unlikely to be altered by dexrazoxane use, although the drug has not been shown to improve progression-free and overall patient survival. At present, the cardioprotective efficacy of dexrazoxane in patients with childhood malignancies is supported by limited data. The drug is generally well tolerated and has a tolerability profile similar to that of placebo in cancer patients undergoing anthracycline-based chemotherapy, with the exception of a higher incidence of severe leukopenia (78% vs 68%; p < 0.01). Dexrazoxane is the only cardioprotective agent with proven efficacy in cancer patients receiving anthracycline chemotherapy and is a valuable option for the prevention of cardiotoxicity in this patient population.

Anthracyclines↗
PubMed1992

Influence of dry heat treatment and anticoagulant on coupling of fibrinogen and fibronectin to von Willebrand factor in normal plasma.

In plasma from healthy subjects a coupling was identified between von Willebrand factor (vWf), fibrinogen (fg), and fibronectin (fn) that was dependent of anticoagulants heparin, EDTA, and citrate. Binding was quantitated by ELISA methodologies, based on polyclonal antibodies directed against the proteins studied, in order to express the percentage of moles of fg or fn bound to moles vWf, C[fg/vWf] or C[fn/vWf] (mol/mol)%. The intra-assay coefficients of variation (CV%) for fg and fn bound to vWf were 10.6% and 7.4% (n = 10) respectively, and the inter-assay coefficients of variation were 24.4% and 22.2% (n = 10). The largest degree of coupling was found in heat-treated lyophilized heparin plasma, where C[fg/vWf] and C[fn/vWf] were 12.9 +/- 1.4 (mol/mol)% and 2.4 +/- 0.1 (mol/mol)% (mean +/- SD). Binding was further qualitatively demonstrated through experiments using gel filtration chromatography and agarose gel electrophoresis followed by immunoblotting. In all instances coupling of vWf with fg was higher than with fn. Lyophilisates of normal plasma that were subjected to dry heating (60 degrees C in 72 h) showed considerably increased coupling. Previous investigators, studying reconstituted factor VIII concentrates by means of gel filtration, pointed out that an association between vWf, fg and fn was present in such therapeutic material. This investigation signifies that a coupling between these proteins may be present even in the source plasma, and that 'dry heating' increases binding. Implications of these results are discussed.

Anticoagulants↗
PubMed1990

Model studies of the iron-catalysed Haber-Weiss cycle and the ascorbate-driven Fenton reaction.

Complementary hydroxylation assays and stopped-flow e.s.r. techniques have been employed in the investigation of the effect of various iron chelators (of chemical, biological and clinical importance) on hydroxyl-radical generation via the Haber-Weiss cycle and the ascorbate-driven Fenton reaction. Chelators have been identified which selectively promote or inhibit various reactions involved in hydroxyl-radical generation (for example, NTA and EDTA promote all the reactions of both the Haber-Weiss cycle and the ascorbate-driven Fenton reaction, whereas DTPA and phytate inhibit the recycling of iron in these reactions). The biological chelators succinate and citrate are shown to be relatively poor catalysts of the Haber-Weiss cycle, whereas they are found to be effective catalysts of .OH generation in the ascorbate-driven Fenton reaction. It is also suggested that continuous redox-cycling reactions between iron, oxygen and ascorbate may represent an important mechanism of cell death in biological systems.

Ascorbic Acid↗
PubMed1993

Spin trapping study of superoxide production in ferrous ion oxidation.

The oxidation of Fe2+ was investigated by electron paramagnetic resonance (EPR) spin trapping techniques with N-t-butyl-alpha-phenylnitrone (PBN) and dimethyl sulfoxide. Under pure oxygen, the spin adduct PBN/.OCH3 was rapidly generated by the addition of Fe2+ (0.2-1.2 mM) into phosphate buffer containing ethylenediaminetetraacetate (EDTA), dimethyl sulfoxide and PBN at pH 7.4, but it decayed. The decay process of PBN/.OCH3 consists of two components. The fast decay was dependent on Fe2+ concentration. Another was due to destruction of the spin adduct by superoxide anion (.O2-), because superoxide dismutase (SOD) markedly prevented the decay. Catalase decreased the yield of PBN/.OCH3. When Fe(3+)-EDTA and ascorbate were used instead of Fe(2+)-EDTA, similar phenomena were detected. These results demonstrate that Fe2+ reacts with O2 to generate .O2-, then H2O2, which produces .CH3 by the reaction with Fe2+ and dimethyl sulfoxide. The .OCH3 radical results from the reaction between .CH3 and O2. The adduct PBN/.OCH3 decays by the reaction with Fe2+ and .O2-.

Ascorbic Acid↗
PubMed1995

N,N'-bis-dibenzyl ethylenediaminediacetic acid (DBED): a site-specific hydroxyl radical scavenger acting as an "oxidative stress activatable" iron chelator in vitro.

During oxidative stress, iron traces are supposed to be released from normal storage sites and to catalyse oxidative damage by Fenton-type reactions. This type of damage is difficult to prevent in vivo except by the use of strong iron chelators such as deferoxamine (affinity constant for Fe(III): log K = 30.8). However, strong iron chelating agents are also suspected to mobilize iron from various storage and transport proteins thereby leading to toxic effects. In contrast, N,N'-bis-dibenzyl ethylenediaminediacetic acid (DBED) is an iron chelator with relatively low affinity for iron (affinity constant for Fe(III): log K < 15). In the present paper, we show that, in situations mimicking oxidative stress in vitro, DBED is site-specifically oxidized into new species with strong iron binding capacity. Indeed, in the presence of ascorbate as a reductant, the iron chelate of DBED reacts with H2O2 in aqueous solution to yield a purple chromophore with minor release of free HO. in the medium, as measured by aromatic hydroxylation assay. The formation of these purple species is not suppressed by the presence of HO. scavengers at high concentration. The visible spectrum of these species is consistent with a charge transfer band from a phenolate ligand to iron. N-2-hydroxybenzyl N'-benzyl ethylenediaminediacetic acid (HBBED) was identified in the medium as one of the oxidation products of DBED. Therefore, these results suggest that the iron chelate of DBED undergoes an intramolecular aromatic hydroxylation by HO. leading to 2-OH derivatives and hence that DBED is a site-specific HO. scavenger. Moreover, since the measured affinity for Fe(III) of HBBED (log K = 28) is at least 13 orders of magnitude higher than that of DBED and since ferric HBBED chelate is not a catalyst of Fenton chemistry, DBED may be looked as an "oxidative stress activatable" iron chelator, e.g. which increase in affinity for iron is triggered in the presence of H2O2 and an electron donor. Therefore it is proposed that DBED and related derivatives may be interesting as protective compounds against oxygen radicals toxicity, especially for chronic use.

Ascorbic Acid↗
PubMed2001

Effects of mineral salts and calcium chelating agents on the gelation of renneted skim milk.

The effects of adding CaCl2, orthophosphate, citrate, EDTA, or a mixture of these, to reconstituted skim milk (90 g of solids/kg solution) on the gelation of renneted milk were mediated by changes in Ca2+ activity and the casein micelle. At pH 6.65, the addition of citrate or EDTA, which removed more than 33% of the original colloidal calcium phosphate with the accompanying release of 20% casein from the micelle, completely inhibited gelation. Reformation of the depleted colloidal calcium phosphate and casein in the micelle, by the addition of CaCl2, removed this inhibition. When the minimum requirements for colloidal calcium phosphate and casein in the micelle were met, the coagulation time decreased with increasing Ca2+ activity, leveling off at high Ca2+ activity. The storage modulus of renneted gels, measured at 3 h, increased with increasing colloidal calcium phosphate content of micelles up to a level at which it was approximately 130% of the original colloidal calcium phosphate in the micelles. Further increases in colloidal calcium phosphate by the addition of CaCl2, orthophosphate, or mixtures of these, which did not change the proportion of casein in the micelle, decreased the storage modulus. The gelation of the renneted milk was influenced by Ca2+ activity, the amounts of colloidal calcium phosphate, and casein within the micelle, with the effects of colloidal calcium phosphate and casein within the micelle clearly dominating the storage modulus. These results are consistent with the model of Horne (Int. Dairy J. 8:171-177, 1998) which postulates that, following cleavage of the stabilizing K-casein hairs by rennet, the properties of the rennet gel are determined by the balance between the electrostatic and hydrophobic forces between casein micelles.

Animals↗
PubMed2005

The effects of various antifungal additives on the fermentation and aerobic stability of corn silage.

In 2 consecutive years, whole plant corn was ensiled in laboratory silos to investigate the effects of various silage additives on fermentation, dry matter (DM) recovery and aerobic stability. In yr 1, chopped forage was treated with 1) no additive (untreated, U), 2) Lactobacillus buchneri 40788, 4 x 10(5) cfu/g of fresh forage (LLB4), 3) L. buchneri 11A44, 1 x 10(5) cfu/g (PLB), 4) Biomax 5 (Lactobacillus plantarum PA-28 and K-270), 1 x 10(5) cfu/g (B5), 5) Silo Guard II (sodium metabisulfite and amylase), 0.05% of fresh forage weight (SG), 6) a buffered propionic acid-based additive, 0.1% (Ki-112), 7), sodium benzoate, 0.1% of fresh weight (SB), or 8) potassium sorbate:EDTA (1:1), 0.1% of fresh weight (PSE). Silage treated with LLB4 had the highest concentration of acetic acid compared with other treatments, and yeasts were undetectable in LLB4 ( 210 h.

Acetic Acid↗
PubMed1993

Complexometric determination of clodronate in aqueous solutions and urine.

Three different procedures for the determination of clodronate by means of Th-EDTA-XO or Th-DCTA-XO (XO = xylenol orange) complexes are presented. According to the UV-VIS and 13C NMR measurements, XO is quantitatively replaced by the clodronate anion in the mixed ligand Th-EDTA-XO or Th-DCTA-XO complexes in slightly acidic solutions. This ligand replacement reaction can be applied to the determination of traces of clodronate. Procedures studied involve visual complexometric titration, spectrophotometric titration and conventional spectrophotometric determination. By visual complexometric titration it is possible to determine clodronate directly in human urine with acceptable accuracy and precision in the range 0.5-2.5 mg l-1. By diluting more concentrated urine samples 1:10 with water, samples of up to 80 mg l-1 can be determined with acceptable accuracy and precision. The working range of the method is linear up to 16 mg l-1 in aqueous solutions with the RSD-value varying between 0.7 and 3.8%. Interference caused by the major substances of human urine on the determination were studied.

Chelating Agents↗
PubMed1998

In vitro attachment of Salmonella typhimurium to chicken cecal mucus: effect of cations and pretreatment with Lactobacillus spp. isolated from the intestinal tracts of chickens.

The attachment of radiolabeled Salmonella typhimurium 333/O cells to immobilized cecal mucus from specific-pathogen-free leghorn chickens was determined in the presence of D-mannose. The attachment of S. typhimurium was inhibited by the chelating agents EDTA and citrate and by lanthanum but was enhanced in the presence of the calcium, barium, and manganese divalent cations. Summary findings of the effect of lectins are included. Attachment of lactobacilli, previously isolated from the intestines of chickens, to mucus was also enhanced by calcium and inhibited by chelators. The pretreatment of immobilized mucus with portions of cultures of five of eight strains of lactobacilli inhibited subsequent attachment of the S. typhimurium strain. Spent culture supernatant fluid and/or washed cells from these cultures inhibited attachment, and inhibition was enhanced by preheating the cells or supernatant fluid at 80 degrees C. Results indicate that S. typhimurium mucus attachment not involving mannosyl-dependent receptors is influenced by presence of cations. Lactobacillus spp. isolated from the intestinal tracts of chickens produce cellular and cell-free components that inhibit this form of attachment to chicken intestinal mucus.

Animals↗
PubMed1978

Labetalol in the treatment of hypertensive renal patients.

The efficacy of labetalol in lowering blood pressure was assessed in 18 patients with chronic renal failure and hypertension. Before the start of labetalol therapy, all patients were receiving combined antihypertensive therapy, the most common being a beta-blocker and hydrallazine. Over the period of about four weeks labetalol was substituted for the prior therapy. 51Cr edetic acid (EDTA) estimations of glomerular filtration rate were performed before labetalol therapy, and then again after one and six months. Before the therapy with labetalol, 12 of the 18 patients had supine diastolic blood pressures of 100 mm Hg or more. At six months, 14 patients remained in the trial and, of these, only four had a supine diastolic blood pressure of 100 mm Hg or more. In the supine position there was a significant reduction of systolic, but not of diastolic, blood pressure. However, in the erect position there was a significant reduction both in systolic and in diastolic blood presure. Pulse rate did not vary significantly. Few side effects were encountered, transient postural dizziness being the most common side effect. Labetalol seems to be an effective substitute for the beta-blocker plus hydrallazine therapy. However, it is not as potent as minoxidil.

Adrenergic beta-Antagonists↗
PubMed1984

The detection of a platelet-agglutinating factor in thrombotic thrombocytopenic purpura.

A sensitive and specific test was used to identify a platelet-agglutinating factor in sera from patients with thrombotic thrombocytopenic purpura. Serum from patients plus a preparation rich in large multimers of factor VIII: von Willebrand factor were added to target platelets, and agglutination occurred in 41 of 48 samples. Edetic acid, heparin, or heating, but not aspirin, monomeric IgG, or dansylarginine N-(3-ethyl-1,5-pentanediyl)amide inhibited the platelet-agglutinating factor. In-vitro agglutination requires the presence of a platelet-agglutinating factor and large multimers of von Willebrand factor. High concentrations of either component lowers the amount of the other required for platelet agglutination. Some patients may be more susceptible to the agglutinating factor because of a congenital or acquired abnormality in processing unusually large multimers of von Willebrand factor or because of infections or inflammatory disorders that lead to increased synthesis of large multimers of von Willebrand factor.

Adult↗
PubMed1997

Antioxidative and chelating activities of phenylpropanoid glycosides from Pedicularis striata.

AIM: To study the antioxidative and iron chelating activities of phenylpropanoid glycosides (PPG) isolated from a Chinese herb Pedicularis striata. METHODS: Antioxidative effects of PPG on lipid peroxidation induced by FeSO4-edetic acid in linoleic acid were measured by thiobarbituric acid method. Chelating activities of PPG for Fe2+ were tested by differential spectrum method. RESULTS: The reaction rates (A532.min-1) of lipid peroxidation were 0.0046 in the control, 0.0021 in verbascoside group, and 0.0008 in isoverbascoside group. The chelating activity of isoverbascoside was 2-fold stronger than that of verbascoside. Permethyl verbascoside showed neither antioxidative nor chelating activities. CONCLUSION: The inhibitory effects of PPG with phenolic hydroxy groups on lipid peroxidation are owing to their chelating properties. Under physiological condition PPG-Fe2+ chelates are sufficiently stable. Thus PPG are able to inhibit the Fe(2+)-dependent lipid peroxidation in vivo through chelating Fe2+ and exhibit their therapeutic potential by the same mechanism in vitro.

Antioxidants↗
PubMed1999

Hydrolysis of extracellular adenine nucleotides by cultured bovine endocardial endothelial cells.

AIM: To characterize the ATP diphosphohydrolase (apyrase) of bovine endocardial endothelial cells, and to compare ecto-adeninenucleotidase activity between bovine endocardial and aortic endothelial cells (BEEC and BAEC). METHODS: The nucleotide was analyzed by reversed phase HPLC and apyrase activity was assayed by inorganic phosphate release. RESULTS: Apyrase inhibitors, both NaN3 10 mmol.L-1 and NaF 20 mmol.L-1, inhibited BEEC apyrase activity by 51% and 38%, respectively. The inhibitor for Na+/K(+)-ATPase, ouabain, did not affect the enzyme activity. Edetic acid 5 mmol.L-1 completely inhibited the enzyme activity. H2O2 0.5 mmol.L-1 downregulated BEEC apyrase activity in a time-dependent manner. The apyrases activities in BAEC were higher than those in BEEC, while the ecto-AMPase activity in BAEC was much weaker than that in BEEC. CONCLUSION: BEEC have NaN3- and NaF-sensitive, ouabain-insensitive apyrase activity. BEEC had high ecto-AMPase activities, and low apyrases activities as compared with BAEC.

Animals↗
PubMed1978

Some properties of deoxycholate and dodecyl sulphate in relation to macroionic complexes and their biochemical implications.

The present communication describes new properties and re-explores some poorly understood characteristics of deoxycholate (DOC, bile salts) and dodecyl sulphate (SDS). These anionic detergents form complexes with basic compounds including drugs and biologically important compounds; the excess of the reagents generally dissolves a complex. A variety of two-component macroionic complexes involving oppositely charged compounds are also dissolved by these reagents. This process implies the dissociation of a complex into its constituent components by DOC/SDS. This would suggest a new attribute of the anionic detergents of breaking up ionic linkages involved in macroionic complexes. This technique makes it possible to obtain quantitative information on the behaviour of binary macroionic complexes. The newly explored characteristics of bile salts might even operate in vivo and thereby explain some of their harmful effects in disorders associated with their elevated levels in vivo. An interference with the action of drugs by bile salts could be another side effect of the latter in the relevant pathological conditions.

Chemical Phenomena↗